Wednesday, 31 December 2014

Cilia,
microscopic, tentacle-like extensions from biological cells, have risen from
relative obscurity and are now considered important to the understanding of
many human afflictions. Ciliopathies often make themselves known as syndromes
with widely varying effects on a number of tissue types. This is the subject of
a new study.

There
are number of human diseases in which cilia may play a role; for example, some
cancers and neurological diseases may be related to ciliopathies. Because of
the limitations placed on research involving humans, the authors propose the
use of model species ranging from the green alga Chlamydomonas to the house
mouse to further study the role of cilia. The study authors write, "We can
anticipate that new and improved techniques will open new avenues for gaining further
insight into these immensely important and ever more fascinating cell
organelles."

Tuesday, 30 December 2014

Gut microbes appear to influence the development of the blood-brain barrier in mice, before and soon after they’re born, according to a study published in Science Translational Medicine.

“It’s absolutely fascinating to think that gut bacteria can control permeability of the blood-brain barrier,” Caltech microbiologist Sarkis Mazmanian, who was not involved in the study, told The Scientist.

The blood-brain barrier (BBB), which shields the organ from blood-borne infections, toxins, and more, is created by steadfast connections called tight junctions between the endothelial cells that line its blood vessels. So effective is the barrier that most proteins and molecules cannot pass through; those that do generally require selective transport via specific receptors.

A similar barrier—made up of epithelial cells and tight junctions—lines the intestine and stops the trillions of microbes present in the gut from escaping into the body. It’s known that the gut bacteria themselves control integrity of this intestinal barrier, said Sven Pettersson of the Karolinska Institute in Sweden who led the new study.

The team compared development of the BBB between germ-free fetal mice and those with normal microbiomes. As expected, the mice with normal microbiomes exhibited normal closure of the BBB toward the late stages of fetal development—a traceable antibody that could be detected readily entering the brain in the early fetus became restricted to blood vessels later on. In the fetuses whose mothers were germ-free, however, the antibody continued to enter brain tissue even late in pregnancy.

This increased barrier permeability was associated with low expression and disorganization of tight junction proteins and was shown by additional methods to persist into adult life. That is, pups that were born to germ-free mothers and that remained germ-free throughout life had leakier BBBs as adults.

Monday, 29 December 2014

New drugs and treatment strategies will be developed from research that provides a new understanding of how bacterial toxins target human cells.

Cholesterol-dependent cytolysins (CDCs) are toxins produced by major bacterial pathogens, most notably Streptococcus pneumoniae and group A streptococci, which collectively kill millions of people each year.

The toxins were thought to work by interacting with cholesterol in target cell membranes, forming pores that bring about cell death.

Bacteria invest energy into creating these toxins because they act as virulence factors. By targeting immune cells such as macrophages the bacteria will be protected against phagocytosis and destruction by respiratory burst. The presence of cholesterol in the membrane of the target cell is required for CDC pore formation. The arrangement of cholesterol molecules in the bilayer is important for successful binding.

Published in the journal Proceedings of the National Academy of Sciences, the research is an international collaboration between Professor James Paton from the University of Adelaide in South Australia and Professor Michael Jennings from Griffith University, and collaborators at the University of Queensland and Department of Microbiology, New York University School of Medicine.To access, go to PNAS

Sunday, 28 December 2014

A new paper of interest by Sofija Petkovska1 and Biljana Gjorgjeska, in relation to food hygiene control, published in Journal of Hygienic Engineering and Design.

The abstract reads:

The usage of different disinfectants in the food and pharmaceutical industry provides a possibility for application of certain level of assurance related to microbiological cleanness by using different types of disinfectants which have different spectrum of operation. Used disinfectants residues which stay on the critical points of the equipment after cleaning become potential contaminants of the products and they can be unsafe for the users’ health. Because of this reasons, the Good Manufacture Practice standards recommend validation of the production equipment cleaning procedures including the aspects of microbiological cleanness
and determination of residues of disinfectants.

According to the Republic of Macedonia regulation acts, an application of HACCP system is recommended which will provide safe food with good quality. The methods and control points described in the general principles of this standard are internationally recognized and are from essential meaning. We would recommend in the control of the residues of disinfectants the general principles of HACCP to be used together with the principles of Good Manufacture Practice (GMP) which is well known standard recommended for pharmaceutical production. The validation plan should include determination of the residue quantity of the disinfectant after cleaning with the disinfectant used. The control method for determination of the residue quantity depends on the chemical characteristics of the disinfectant used. In general, specific methods that are sensitive and give possibility for the detection and quantification of selected disinfectant should be used.

Saturday, 27 December 2014

In the guide, the authors discuss trends in single-use
bioreactors, disposable chromatography, and best practices for reducing
particulates in single-use systems. In addition, budgeting and sourcing
single-use components from multiple suppliers is explored. The latest
technologies introduced for single-use applications are also explored.

Friday, 26 December 2014

The editors of Pharmaceutical Technology review best practices
and methods for analytical and bioanalytical testing. Topics include method
transfer during scale up, viral contamination detection, analytical quality by
design, screening methods for compliance with USP <232>, and validation
of a bead-based multiplexed kit for quantification of nine different cytokines.
A roundup of analytical instruments, systems, and software introduced in 2014
will be included.

Issue topics include:

Rapid Screening of Pharmaceutical Materials for Compliance with
USP<232> using ICP-MS

Validation of a Multiplex Bead-Based Assay for the
Quantification of a Panel of Nine Cytokines to be used for Clinical Sample
Analysis

Thursday, 25 December 2014

Biologists
have described the complex relationships within an ecosystem through a new
model. The model ecosystem was a “biological wastewater treatment plant”. In it
live numerous species of bacteria which are involved in the wastewater
purification process.

For
the analyses of the treatment plant ecosystem, the researchers employed Systems
Biology methods. Wastewater destined for treatment comprises energy-rich
substrates including fats, proteins, carbohydrates and many other substances
that serve as nutrients for the resident bacteria. Every wastewater treatment
plant is therefore a complex ecosystem.

The
basis for this are the so-called "omics" -- genomics,
transcriptomics, proteomics and metabolomics -- combined with new bioinformatic
methods for integrated data analysis.

There
is one species of bacteria that stands out and has grabbed the researchers'
attention: Microthrix parvicella, whose genome sequence the LCSB group
first decrypted two years ago. This bacterium can absorb and store an
especially large amount of lipids. In winter, up to 50 percent of all bacteria
on the surface of treatment tanks belong to this species.

The
implication is that the lipids from wastewater stored in the bacteria are a
renewable energy source since they can be easily converted into biodiesel.

Tuesday, 23 December 2014

A healthy dose of microbes are swapped between kissing couples, according to a study published in Microbe.

Researchers in Amsterdam swabbed the mouths and collected saliva from 21 couples visiting a zoo in the city both before and after they shared 10-second kiss. They found that the couples tended to have similar microbes inhabiting their mouths, likely because they share kisses, food, and space on a regular basis.

Apparently, being with somebody for an extended amount of time and having a relationship leads to a similar collection of bacteria on the tongue (reference: Time.)

When the researchers had one partner sip a probiotic yogurt drink, which contains bacteria not normally present in the mouth, prior to kissing their mate again, they found that an average of 80 million bacteria were swapped between kissers.

Monday, 22 December 2014

UK
Science & Innovation Network, India and the Royal Society of Chemistry have
put together a report of interest. The report is titled: “Report on the UK-India
Workshop and Roundtable on Mitigating Anti-microbial Resistance (AMR) and
Controlling Infectious Diseases.”

The
report is based on a meeting between the two bodies.

The
key finding is:

“R&D
in Central Nervous System (CNS) and antimicrobials has decreased significantly
over the last 20 years globally. There is declining interest among Indian and
global pharma companies to undertake research in AMR drug discovery due to the
long gestation period, low returns and lack of expertise. For example, most
drug discovery chemists do not understand the biology of the disease. There are
fewer number of infectious diseases biologists in India.”

Sunday, 21 December 2014

The ability to move enables many mycoplasmas and bacteria to reach
a specific niche or to leave hostile environments. The organism Mycoplasma gallisepticum is a poultry
pathogen that is capable of gliding over solid surfaces. Scientists have now
identified the proteins responsible for this gliding mechanism.

Mycoplasma gallisepticum is related to the human
pathogen Mycoplasma pneumoniae, the
causative agent of human bronchitis and pneumonia. Researchers have found that
its abilityto glide requires the proteins GapA, CrmA and Mgc2.

Saturday, 20 December 2014

One
of the world's most prolific bacteria, Pseudomonas
aeruginosa, manages to afflict humans, animals and even plants by way of a
mechanism not before seen in any infectious microorganism -- a sense of touch. Pseudomonas is the first pathogen found
to initiate infection after merely attaching to the surface of a host.

The
researchers found, however, that the bacteria could not infect another organism
when a protein on their surface known as PilY1 was disabled.

To
demonstrate the bacteria's wide-ranging lethality, Siryaporn infected ivy cells
with the bacteria then introduced amoebas to the same sample; Pseudomonas
immediately detected and quickly overwhelmed the single-celled animals.

Friday, 19 December 2014

More
and more infections in Europe are proving able to evade even the most powerful
antibiotics, posing an alarming threat to patient safety in the region, health
officials said recently.

Releasing
annual data on antibiotic resistant superbugs, the European Centre for Disease
Prevention and Control (ECDC) said bacterial infections resistant to
carbapenems - a major last-line class of antibiotics used to treat
hospital-acquired superbugs - are ever more common in the European Union.

"With
a smaller number of effective antibiotics, we are gradually returning to the
'pre-antibiotic era' when bacterial diseases could not be treated and most
patients would die from their infection," said Marc Sprenger, the ECDC's
director.

The
Stockholm-based ECDC also said it had for the first time collected data on
resistance among infections caused by a bacteria called Klebsiella pneumoniae
to a powerful but older antibiotic known as colistin - and had found alarming
signs.

"According
to our data, resistance to colistin was observed in 5% of Klebsiella pneumoniae
isolates for the EU overall," Sprenger said.

Klebsiella
pneumoniae is a common cause of pneumonia, urinary tract and bloodstream
infections in hospital patients. If antibiotics are unable to treat them
effectively, patients can face long, costly stays in hospital, and risk dying.

Colistin
is a last-resort antibiotic developed several decades ago that has serious side
effects and limitations to its use, but has become essential for treating
carbapenem-resistant Klebsiella pneumoniae infections.

Drug
resistance is driven by the misuse and overuse of antibiotics, which encourages
bacteria to evolve to survive and develop new ways of beating the drugs.

It
has been a feature of medicine since Alexander Fleming's discovery of
penicillin in 1928, but has become a major global health threat as new drug
development has failed to keep pace with the bugs' ability to develop
resistance to them.

The
ECDC data showed an increase of carbapenem resistance in Klebsiella pneumoniae
to a population-weighted EU average percentage of 8.3% in 2013 from 4.6% in
2010.

Vytenis
Andriukaitis, Europe's commissioner for health and food safety, said the near
doubling of resistance in some bacteria in three years was "truly
alarming" and illustrated the need to tackle the issue from all
directions.

"Antimicrobial
resistance is one the most pressing public health issues of our time," he
said in a statement as the data were published.

Thursday, 18 December 2014

A
new report which sets out the foundation for future research into
anti-microbial resistance (AMR) has been published by the Medical Research Council
(MRC). The report tells the story of key research achievements over the
past thirty years, showcasing some of the best advances and providing the
groundwork for a cross-Council collaboration on AMR research.

Antimicrobial
resistance is a huge and complex problem for healthcare and agriculture.
Antibiotics have been used to treat bacterial infections in humans and animals
for 70 years, but these medicines are becoming less and less effective. No new
classes of antibiotics have been discovered for 25 years and some strains of
bacteria are now unharmed by the drugs designed to kill them.

In
the UK alone £275 million has been spent on research in this area since 2007,
yet, to date, no effective solutions have been found. It has been estimated
that current antibiotics may be useless within the next two decades.

The
UK Research Councils have joined together in an historic initiative to tackle
this global problem. Coordinating a network of medical researchers, biologists,
engineers, vets, economists, mathematicians and designers, the MRC will help to
drive through new discoveries and advancements.

The
AMR initiative, which has been heralded as a war cabinet for AMR research,
pulls together all seven research councils and looks to deliver exciting new
research projects on four fronts:

Understanding
resistant bacteria in the context of the host.

Accelerating
therapeutic and diagnostics development.

Understanding
the real world interactions.

Behaviour
within and beyond the health care setting.

The
report published today offers a timeline and case studies in each area
supported by the Biotechnology and Biological Sciences Research Council
(BBSRC), Engineering and Physical Sciences Research Council (EPSRC) and the
Medical Research Council (MRC). From how American Bullfrogs might help to treat
wounds infected with MRSA, to how a smartphone app helps healthcare professionals
choose the best course of treatment to ensure antimicrobials are prescribed
appropriately, the report provides a shop window on AMR research.

Dr
Des Walsh, Head of Infections & Immunity at the Medical Research Council
(MRC) said: “Years of research mean that we are now in a better position than
ever to get to the bottom of how and why some bugs are resistant to
antibiotics. But we need to understand AMR at every level and in every
environment – from labs to livestock, from finding new diagnostic tools to
educating professionals and the public, which is why the MRC is leading the
Funders’ Forum and working with all of the research councils providing millions
in support to the best research projects designed to beat this problem.”

Wednesday, 17 December 2014

Research suggests that alcohol wipes are capable of destroying the widest range of microbial contamination
(including Mycobacteria, the genus of bacteria that includes the infectious cause of tuberculosis). Alcohol wipes are virucidal against ‘enveloped’ viruses, such as HIV and hepatitis B and against the ‘non-enveloped’ viruses, such as poliovirus, rhinoviruses and hepatitis A. However, in addition to microbial contamination, surfaces may also be contaminated with protein residues such as blood and pus. It has been suggested that alcohol may bind protein to stainless surfaces and the presence of protein may compromise the efficacy of alcohol based wipes.

This issue is the basis of an article by Tim Sandle. The reference is:

Sandle, T. (2014) Are alcohol wipes effective in the presence of protein?, The Dentist, October 2014, pp92-94

A similar article,. outlining good cleaning practices has also been published:

Tuesday, 16 December 2014

Chapter
5.1.1 of the European Pharmacopeia is undergoing review and a draft has been
published in Pharm Europa, titled “Methods of Preparation of Sterile Products.”

In
relation to the changes:

In
the introduction, the reference to GMP has been removed;

In
the section Sterility assurance level, the reference to exponential
inactivation has been removed as membrane filtration is not a first order
process;

The
sections on the different sterilisation processes, where appropriate, now have
the same format: principle, equipment, sterilisation cycle, cycle effectiveness
and routine control; where required, relevant information has been added;

Modern
concepts for validation of steam sterilisation have been added;

A
wider description of the equipment suitable for dry heat sterilisation has been
provided;

In
the section Ionising radiation sterilisation, the reference to European Notes
for Guidance

has
been removed;

In
the section Gas sterilisation, two different types of agents are defined:
alkylating agents and oxidising agents. The establishment of the cycle
effectiveness has been described in more detail;

In
the section Membrane filtration, the description of the microbial challenge
test has been removed as it is proposed for inclusion in the revised chapter on
biological indicators;

In
the section Aseptic preparation, freeze-drying under aseptic conditions is
added.

Monday, 15 December 2014

Spectrophotometric particle counters are the main item of
cleanroom monitoring technology to have emerged in recent years. The counters
can differentiate inert particles from ‘biologic’ particles (where biologic may
indicate a microorganism). This article outlines a summary of a study that
examined the application of spectrophotometric particle counters for the risk
assessment of a cleanroom that underwent deactivation and reinstatement
cleaning. The study demonstrates how establishing a particle and biologic
particle baseline can provide useful information to compare the environmental
condition of a cleanroom pre- and post-maintenance shutdown.

This is the basis of a new article by Tim Sandle for Clean Air
and Containment Review. The reference is:

The current issue also features a discussion on the application
of ventilation equations to cleanrooms, by Bill Whyte and colleagues; a
discussion on the chemical influence on ISO 14644 standards by Dick Gibbons;
the history of isolator technology by Doug Thorogood; and the history of ultra
clean operating theatres by Amanda Parkin…and more.

A study was undertaken to compare microbial recoveries from pharmaceutical-grade cleanrooms using two different incubation regimes and a general-purpose agar (Tryptone Soy Agar). One temperature regime (A) incubated plates first at 30 degrees C to 35 degrees C, followed by 20 degrees C to 25 degrees C; the second temperature regime (B) began the incubation with plates at 20 degrees C to 25 degrees C, followed by 30 degrees C to 35 degrees C. The experimental outcomes demonstrated that there was no significant difference with the total microbial count when measured using a t-test (0.05 significance level; 95% confidence interval). However, with the recovery of fungi, the second incubation regime (B), which began with the lower 20 degrees C to 25 degrees C temperature, produced higher incidents and numbers of fungi. While this finding might provide the basis for adopting one incubation regime over another, a review of the types of cleanrooms recovering fungi suggests that fungal incidents are low, and they are more often confined to specific areas. Thus, as an alternative, incubation regimes could be varied to suit different cleanroom environments or a selective mycological agar adopted for specific areas.

About half of the H3N2 influenza samples tested in the United States encode altered antigens from the strain used to produce this year’s vaccine.

While widespread vaccination is still the best defense against the influenza virus, the US Centers for Disease Control and Prevention (CDC) warned recently that many of this year’s circulating strains are different from the ones used to formulate the annual flu vaccine.

So far this season, more than 90 percent of the reported flu cases in the US are of the H3N2 subtype, and 52 percent of the samples tested have mutations in antigen-encoding genes compared to the sample used to produce the annual vaccine.

Saturday, 13 December 2014

Keeping
healthcare facilities clean is an issue of great importance. In an interesting
review for Controlled Environments, outlines some of the key issues for the
avoidance of microbial contamination. These are:

1.Housekeeping
– “Bacteria and germs can hide in surprising places: one national study found
that soap dispensers – more specifically, the nozzle users press to obtain soap
– harbored more bacteria and germs than toilet seats.”

2.Plant
maintenance – “In 2001 the largest historic outbreak of Legionnaire’s disease
is estimated to have sickened more than 800 in Murcia, Spain. Subsequent
investigation linked the outbreak to a hospital cooling tower.”

3.Codes
or a higher standard of care – “In designing new or renovated healthcare
spaces, serious consideration should be given to the level of desired design,
based upon the function of the space, its clinical program, and the risk of
HAIs.”

4.Humidity
control – “Humidity levels play a major role in maintaining health and avoiding
impacts from bacteria, viruses, fungi, mites, molds, and chemical interactions.”

5.Air
– “The pinnacle of superior air quality depends upon the volume of new air
circulating in a space, dilution, carefully calibrated filtration and, where
appropriate, either positive or negative pressurization.”

Friday, 12 December 2014

Antibiotic
drugs save lives. But we simply use them too much — and often for
non-lifesaving purposes, like treating the flu and even raising cheaper
chickens. The result, says researcher Ramanan Laxminarayan, is that the drugs
will stop working for everyone, as the bacteria they target grow more and more
resistant. He calls on all of us (patients and doctors alike) to think of
antibiotics — and their ongoing effectiveness — as a finite resource, and to
think twice before we tap into it. It’s a sobering look at how global medical
trends can strike home.

The
hazard with regard to details of bacterial resistance patterns in relevant
microorganisms in vitro may be characterised by providing: – Minimum inhibitory
concentration (MIC) data of the antibacterial agent against bacterial species likely
to be affected. MIC distribution data should be presented for targeted
bacterial species and for relevant non-targeted bacterial species. Estimated
rates of development of the expression of resistance, such as indicated from in
vitro studies of passaged microorganisms in the presence of the antibacterial
agent, may be included. – Details of microbial resistance patterns in relevant
human isolates which have emerged with the use of the antibacterial agent, or
related substances, overseas and/or in Australia should be provided when
available. This would include changes identified in MICs of the antibacterial
agent against isolates of bacterial species likely to be affected collected
from clinical trials or from wider clinical use. The risk assessment should
state whether Australian data are included and Australian data should be
provided where available and recent. Interim guideline on antibacterial
resistance risk data

Data
on mechanisms of resistance pathways in relevant microorganisms.

Data
on in vitro cross-resistance with other antibacterial agents in the same class
in targeted and non-targeted bacterial species.

Wednesday, 10 December 2014

In
a perspective piece published in the journal Science, Eddy Rubin,
Director of the U.S. Department of Energy Joint Genome Institute (DOE JGI), a
DOE Office of Science User Facility, along with Microbial Program Head Tanja
Woyke, discusses why the time is right to apply genomic technologies to
discover new life on Earth. In this perspective they propose the division of
microbial life on Earth into three categories: explored, unexplored, and
undiscovered. The first can be grown in the laboratory. The second encompasses
the uncultivated organisms from environmental samples known only by their
molecular signatures. The third, the focus of the perspective, is the
yet-undiscovered life that up until now has eluded detection.

Tuesday, 9 December 2014

The
World Health Organization (WHO) is revising its guidance on non-sterile
processing validation. The guidance is titled “Revision of the Supplementary
Guidelines on Good manufacturing Practice: Non-sterile process validation.”

The
process of updating began in 2013. In August 2014 a new draft was circulated
for comments. The final version is expected early in 2015.

Process
validation data should be generated for all products to demonstrate the
adequacy of the manufacturing process. The validation should be carried out in
accordance with GMP and data should be held at the manufacturing location
whenever possible and be available for inspection.

Central
to the guidance is risk assessment, as the guidance states: “risk-based
approach in validation is recommended. The use of in-line, online and/or
at-line controls and monitoring are recommended to ensure that a process is in
a state of control during manufacture.”

Sunday, 7 December 2014

ABC
Transporters are proteins that are embedded in the cell membrane and facilitate
the transport across cellular barriers not only of an almost unlimited variety
of toxic substances, but also of substances that are essential for life. They
also play a role in the development of antibiotic resistance. A research group
has now succeeded in elucidating the detailed structure of this transporter.